Appearance of immature/transitional B cells in HIV-infected individuals with advanced disease: Correlation with increased IL-7

Abstract

Progression of HIV disease is associated with the appearance of numerous B cell defects. We describe herein a population of immature͞transitional B cells that is overly represented in the peripheral blood of individuals with advancing HIV disease. These B cells, identified by the expression of CD10, were unresponsive by proliferation to B cell receptor triggering and possessed a phenotype and an Ig diversity profile that confirmed their immature͞ transitional stage of differentiation. Consistent with an immature status, their lack of proliferation to B cell receptor triggering was reversed with CD40 ligand, but not B cell activation factor. Finally, levels of CD10 expression on B cells were directly correlated with serum levels of IL-7, suggesting that increased levels of IL-7 modulate human B cell maturation either directly or indirectly by means of a homeostatic effect on lymphopenia. Taken together, these data offer insight into human B cell development as well as B cell dysfunction in advanced HIV disease that may be linked to IL-7-dependent homeostatic events.immunopathogenesis ͉ CD10 ͉ CD21 ͉ B cell receptor ͉ lymphopenia

Loss of Discrete Memory B Cell Subsets Is Associated with Impaired Immunization Responses in HIV-1 Infection and May Be a Risk Factor for Invasive Pneumococcal Disease

“…Increased numbers of transitional B cells are a characteristic feature of several inherited humoral immunodeficiency conditions and may also be seen in HIV infection (21,22). Maturation of transitional B cells is dependent in part on the expression of receptors for TNF superfamily proteins, including B cell-activating factor (BAFF) and a proliferating-inducing ligand (APRIL) (16, 38 -40).…”

“…The ontogeny of IgM memory B cells in humans remains unclear; one suggestion is that this B cell subset may be derived from transitional B cells which are a naive B cell population that need the spleen to complete their development to mature B cells (19,20). Increased numbers of transitional B cells are a characteristic feature of several inherited humoral immunodeficiency conditions and HIV infection (21,22) and are associated with decreased memory B cells (21). Expansion of transitional B cells may reflect increased immune activation which has been linked with impaired T cell-dependent Ag vaccine responses in patients with HIV-1 infection (23,24).…”

Two overrepresented B cell populations in HIV-infected individuals undergo apoptosis by different mechanisms

“…These two B cell populations represented close to 50% of the total B cells in the peripheral blood ( Fig. 1 A), compared with Ͻ15% in HIV-negative and -infected aviremic individuals and Ͼ50% in HIV-infected individuals with more advanced disease (7,11). To determine which of the two overrepresented B cell populations was responsible for the increased susceptibility to CD95L-mediated apoptosis (8), levels of CD95 were measured on each population shown in Fig.…”

“…The homeostatic compensation observed with CD4 ϩ T cell lymphopenia has been reported to be associated with increased serum levels of IL-7 in HIV-infected individuals (15,16). More recently, this IL-7 associated lymphocyte homeostasis has been shown to involve B cells in both HIV and non-HIV immunodeficiencies (11,17). These data suggest that, in contrast to the influence of HIV-mediated immune activation on mature B cell differentiation, the appearance of immature/transitional B cells in HIV disease may be a consequence of HIV-induced lymphopenia.…”

“…Recently, we reported the expansion of immature/transitional B cells in HIV-infected individuals with advancing disease (11). The presence in the peripheral blood of these B cells, defined by the expression of CD10, was first reported to be associated with HIV disease progression almost 20 years ago (12), and more recently has been associated with several non-HIV immunodeficiency disorders (13,14).…”